New data on the potentials and prospects for the use of immobilized enzymes in medicine]

The data on the completing level of a number of medical preparations on the basis of immobilized proteins, in particular, on the basis of enzymes are given. The firms and companies which successfully cooperate in the field of development of commercial programs for such preparations are listed. On the basis of own study a possibility to create some effective antitumor compounds in the next future is shown. The urgent and prospective application of the immobilized enzymes instead of the native ones in the medicine is grounded.     

Multifunctional nanoparticles--properties and prospects for their use in human medicine

A major aim of medicine has long been the early and accurate diagnosis of clinical conditions, providing an efficient treatment without secondary effects. With the emergence of nanotechnology, the achievement of this goal seems closer than ever. To this end, the development of novel materials and devices operating at the nanoscale range, such as nanoparticles, provides new and powerful tools for imaging, diagnosis and therapy. This review focuses on the significant improvements in performance that nanoparticles offer compared with existing technologies relevant to medicine. Specifically, we address the design of multifunctional nanoparticles as an alternative system for drug and gene delivery, which has great potential for therapy in areas, such as cancer and neuropathologies. Moreover, we discuss the controversy generated by the possible toxic health effects of nanoparticles.     

Experimental bases and prospects for the use of humic acid preparations from peat in medicine and agricultural production]

The analysis of action of physiologically active peat substances--a complex of humic acids is given. Using the pharmaco-biological tests and modelling of the diseases a high antitoxic effect of sodium humate and possibility to use it in medicine, veterinary science and animal husbandry as nonspecific pharmacy raising the organism resistance to the action of different unfavourable factors is proved.     

The biological role of mucins in cellular interactions and immune regulation: prospects for cancer immunotherapy

Among the human mucins, MUC1 is unique in its cell-surface transmembrane expression and its apparent signal-transduction functions. The high expression of MUC1 on many human cancers makes it an attractive target for immunotherapy. Immunization of human cancer patients with MUC1 peptides has resulted in the generation of both anti-MUC1 antibody and cytotoxic T lymphocyte responses. Recently, a novel immunoregulatory role for MUC1 has been suggested by experiments demonstrating that soluble MUC1 induces T-cell unresponsiveness, and that T cells appear to express and secrete MUC1 following their activation. MUC1 is an apparent paradox, having both adhesive and antiadhesive functions, and immunostimulatory and immunosuppressive activities.     

Aldose reductase: physiological role, properties and prospects for regulating activity]

Some properties of aldose reductase isolated from various sources and possible ways of regulation of the enzyme catalytic activity are reviewed. Mammalian aldose reductases are monomeric enzymes with M(r) of 30-40 kDa and a broad substrate specificity towards aldoses. The physiological role of this enzyme consists, apparently, in providing an additional pathway for utilization of glucose and removing toxic compounds carrying an aldehyde group from the cell. Aldose reductase is thought to play a key role in various hyperglycemic states, including diabetic cataract. The kinetics of the aldose reductase reaction is hyperbolic with NADPH and nonhyperbolic with glucose. The rate of the enzyme-catalyzed reaction is determined by the effector binding in the active of inhibitory center of the enzyme. Incubation with substrates leads to the activation of the enzyme which is accompanied by a decrease of the effector binding in the enzyme inhibitory center with a sharp decrease in the sensitivity of the activated enzyme to NADPH concentration changes in the presence of glucose excess. A mechanism underlying the catalytic effect of both native and activated forms of the enzyme is proposed.     

Mixed-function oxidase induction as a test for the biological monitoring of water: limitations and prospects]

The induction in fish liver of some enzyme activities, and typically of microsomal mixed-function oxidases (MFO), provides the earliest biological warning signal of exposure to pollutants. Our studies provided evidence that the basal levels of cytochrome P-450 and specific MFO activities, such as arylhydrocarbon hydroxylase (AHH) and ethoxyresorufin deethylase (EROD), were strongly influenced by the diet in freshwater fish (Oncorhynchus mykiss). The response of fish liver to a known enzyme inducer, i.e., beta-naphthoflavone, was also affected by the diet, which therefore should be carefully controlled in laboratory studies. Under field conditions MFO activities were significantly enhanced in the liver of O. mykiss kept in polluted river water as well as in the liver of the seawater fish Diplodus annularis collected from a polluted harbour area, as compared to specimens of the same species collected from an unpolluted reference area.     

Bryostatins: biological context and biotechnological prospects

Bryostatins are a family of protein kinase C modulators that have potential applications in biomedicine. Found in miniscule quantities in a small marine invertebrate, lack of supply has hampered their development. In recent years, bryostatins have been shown to have potent bioactivity in the central nervous system, an uncultivated marine bacterial symbiont has been shown to be the likely natural source of the bryostatins, the bryostatin biosynthetic genes have been identified and characterized, and bryostatin analogues with promising biological activity have been developed and tested. Challenges in the development of bryostatins for biomedical and biotechnological application include the cultivation of the bacterial symbiont and heterologous expression of bryostatin biosynthesis genes. Continued exploration of the biology as well as the symbiotic origin of the bryostatins presents promising opportunities for discovery of additional bryostatins, and new functions for bryostatins.     

Spectroscopic and biological studies of a novel synthetic chlorin derivative with prospects for use in PDT

Photosensitizers with desirable combinations of chemical, photophysical and biological properties are essential for improving the efficacy of photodynamic therapy (PDT) against various cancers. Chlorins seem to be promising candidates for photodynamic therapy (PDT) owing to their photophysical properties. This paper reports spectroscopic and biological properties of a novel synthetic chlorin derivative. Cytotoxicity, phototoxicity as well as subcellular localization of the novel derivative was studied using Lewis lung carcinoma cultured cells (LLC). In the examined concentration range no significant cytotoxic effects were found but high phototoxicity was observed. Confocal laser scanning microscopy demonstrated that the compound, upon entering cells, was localized in the perinuclear cytoplasm of LLC cells. Using fluorescent microscopy we investigated the impact of PDT based on the novel compound upon cytoskeleton and DNA structure of LLC cells. Our results indicate that liposomes are effective in transferring the chlorin photosensitizer into the studied cells, leading to their high photosensitization, whereas the non-carrier delivery mode (i.e., DMSO) is rather useless for such purposes.     

The biological role of estriol]

It was demonstrated on the uteri of women and guinea pigs that estriol (in vitro) possessed a marked affinity to the estradiol-binding system of human and guinea pig uteri; the activity of steroid-receptor interaction of estriol in vitro constituted 9.4% for guinea pigs and 17% for man in relation to the estradiol activity. Administration of estriol to guinea pigs in vivo in a dose of 0.25-0.5 mg led to a sharp reduction of the estradiol-binding capacity of the receptor system of the uterus. It is supposed that there existed a competitive relationship between estradiol and estriol for binding with the active centres of the receptor proteins of the uterus.     

Oribatid mites: prospects for their use in ecotoxicology

Oribatid mites are a group of arthropods that have had remarkable evolutionary success with regard to species richness, variety of habitats colonized, life-cycle variation and reporductive patterns. The aim of this paper is to review some of the important features of Oribatida in relation to the possible use of these animals in ecotoxicological experiments. Their often sedentary way of living, combined with a narrow dependence on microhabitats qualify oribatids as potential indicator organisms for air and soil quality. Some species have been shown to be extremely sensitive to air pollutants such as SO₂ and NO₂. A low metabolic rate may be the driving force for slow development, low fertility, iteroparity and long adult life. Given these life-cycle characteristics, oribatids may be particularly vulnerable to intoxication by persistent contaminants. Work done on heavy metals suggests that the capacity for accumulation differs greatly between species. The camisiid Platynothrus peltifer accumulates high amounts of trace metals, specifically Mn. The toxicity of Cd, Cu and Pb has been studied in P. peltifer, demonstrating the necessity to consider egg production as a sensitive criterion. It is concluded that oribatid mites hold a great potential for use in ecotoxicology, due to the structural and functional complexity of their communities, and several peculiarities not found in other arthropods. The possibilities offered by this diverse group have not yet been fully employed by ecotoxicologists.     

Calcium imaging in the living brain: prospects for molecular medicine

Calcium imaging has revolutionized the approaches for functional analyses in the living brain of animal experimental models. Changes in intracellular calcium concentration are strictly linked to the electrical activity in neurons and produce signals that are effectively detected by optical methods. Distinctive features of fluorescence-based calcium imaging are its high temporal resolution in the millisecond range and its high spatial resolution in the micrometer range. Recent progress includes the development of fluorometric calcium sensors, new approaches for targeted labeling with these sensors and the implementation of powerful imaging techniques, especially two-photon microscopy. An important and rapidly evolving field of current research is the use of calcium imaging for the analysis of in vivo mouse models for various brain diseases, such as Alzheimer's disease, stroke and epilepsy.     

Plasma-desorption mass spectrometry. Study of the desorption mechanism and prospects for use]

Particle impact mass spectrometry and in particular the use of MeV particles as in plasma desorption mass spectrometry (PDMS) applied to biomolecules is described. Experimental and theoretical studies of the mechanisms involved for large molecular ion ejection are treated in some detail. Applications of PDMS mass spectrometry to proteins are discussed.     

Carnosine and anserine as specialized pH-buffers--hydrogen ion carriers]

Data are reviewed that carnosine (pK 6.9) and anserine (pK 7.1) act as specific mobile pH buffers promoting a rapid elimination of pH gradients between different parts of muscle fibers (very large cells containing various structural components, such as actomyosin, Z-discs, mitochondrial and sarcoplasmic reticulum, etc.). The specific role of these muscle dipeptides as pH buffers (H(+)-translocators) provides explanation for the so-called "Severin phenomenon"-a manyfold enhancement by carnosine of the ability of the isolated muscle to contract and accumulate lactate.     

Carnosine and anserine in working muscles--study using proton NMR spectroscopy]

NMR spectroscopy was used to study carnosine and anserine metabolism in rat tissues under intensive muscle loading. Muscle loading was accompanied by the dipeptide (predominantly anserine) accumulation in muscle tissues. Preliminary per os administration of carnosine (250 mg/kg of body mass) did not increase the dipeptide content in muscle tissues but diminished the lactate content in rat muscles under intensive muscle loading.     

Successes and prospects for genetic engineering]

The review of literature (1970-1976) on problems of gene engineering is given. Gene engineering is pointed out to be a new method of modern biology and a new page of modern molecular genetics. Gene engineering detected a real possibility of artificial creating living hybrid organisms, i.e. constructing functional recombinant DNA molecules according to a project of investigator, but not to possibilities of crossing. The determination of gene engineering (in contrast with genetical engineering) is given in the first division of the article. Genetical engineering is a construction of hybrid organisms on the basis of recombination between non-homologous chromosomes cy crossing. Genetical engineering is based on sex crossing, thus the application of this method is restricted by crossability (i.e. experiments in vivo), which possibilities are determined by taxonomical limits. Gene engineering is a new method of operating directly with genes. It permits constructing in vitro any hybrid genomes desirable. There is no limits of combining ability for gene engineering. Three main stages of constructing hybrid genomes should be taken into account for the proper determination of gene engineering as a method of genome constructing: 1) the gene isolation; 2) their cross-linking in vitro; 3) the transfer of hybrid DNA into recipient cell or its genome. The cardinal stage of gene engineering is the construction of hybrid DNA, cross-linking any initial DNAs from any remote animals, plants and bacteria. All the methods known of gene isolation are described. The chemical method of gene isolation is based on that case, when DNA of some gene differs in its physico-chemical characteristics from total DNA, for example, DNAs of genes coding ribosomal RNAs or sea urchine histone DNA. Isolation of promotors and operators using DNA dependent RNA polymerase, which recognizes promotors, repressor and operator DNA, should also be considered as the chemical method of gene isolation. Restrictase method, which is also well known, is convenuent because the restricts have long enough sticky ends, which is important for the following gene cross-linking. The method of total restriction, reported by Lederberg et al. and Debabov et al., is described. The phage method (in particular, Shimada method) is given, permitting the direct integration of lambda phage into a number of sites of Escherichia coli chromosome. Gene engineering method of gene isolation is mentioned, in particular, the data of Kameron et al. on hybrid phages carrying DNA ligase gene, and Clark a. Carbon on hybrid plasmids carrying triptophane and arabinose operons genes. These methods are called "shot gun". Methods of gene isolation from higher organisms are less developed. A method of gene isolation using so called colony hybridization (according to Grünstein and Hognes) is also given...